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| ID | Type | Description | Link |
|---|---|---|---|
| 2010-019375-30 | EudraCT Number |
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This study was a Phase II, single-blind, randomized, placebo-controlled trial to determine whether anti-vWF Nanobody is safe and effective as adjunctive treatment in patients with aTTP.
Patients received either placebo or anti-vWF Nanobody as adjunctive therapy to plasma exchange (PE).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Caplacizumab | Experimental | Caplacizumab 10 mg once daily |
|
| Placebo | Placebo Comparator | Placebo once daily |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Caplacizumab | Biological |
|
| Measure | Description | Time Frame |
|---|---|---|
| Time-to-response of Treatment Defined by a Confirmed Recovery of Platelets ≥ 150,000/µL | Time-to-response, defined by the achievement of platelet count response, confirmed at 48 hours after the initial reporting of this response. Platelet response was defined as recovery of platelets ≥ 150,000/µL. This response had to be confirmed at 48 hours after the initial reporting of platelet recovery ≥ 150,000/µL by a de novo measure of platelets ≥ 150,000/µL and lactate dehydrogenase (LDH) ≤ 2x upper limit of normal (ULN) (i.e., 'confirmed platelet response'). | From the day of first study drug administration up to 30 days after first study drug administration |
| Measure | Description | Time Frame |
|---|---|---|
| Number and Percentage of Subjects With Complete Remission Following Initial Daily Plasma Exchange (PE) | Number and percentage of subjects with complete remission (defined as confirmed platelet count response and absence of exacerbation) following initial daily PE. | From the day of first study drug administration up to 30 days after first study drug administration |
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Inclusion Criteria:
Exclusion Criteria:
Platelet count ≥ 100,000/µL
Severe active infection indicated by sepsis (requirement for pressors with or without positive blood cultures)
Clinical evidence of enteric infection with Escherichia coli 0157 or related organism
Anti-phospholipid syndrome
Diagnosis of disseminated intravascular coagulation (DIC)
Pregnancy or breast-feeding
Hematopoietic stem cell or bone marrow transplantation-associated thrombotic microangiopathy
Known with congenital TTP
Active bleeding or high risk of bleeding
Uncontrolled arterial hypertension
Known chronic treatment with anticoagulant treatment that cannot be stopped safely, including but not limited to:
Severe or life threatening clinical condition other than TTP that would impair participation in the study
Subjects with malignancies resulting in a life expectation of less than 3 months
Subjects with known or suspected bone marrow carcinosis
Subjects who cannot comply with study protocol requirements and procedures
Known hypersensitivity to the active substance or to excipients of the study drug
Severe liver impairment, corresponding to grade 3 toxicity defined by the CTCAE scale. For the key liver parameters, this is defined as follows:
Severe chronic renal impairment, as defined by glomerular filtration rate < 30 mL/min
Note that the use of another investigational drug or device within 30 days prior to screening was not allowed. Participation in non-interventional/observational studies and registries during the study period was allowed. Participation in another clinical study was not allowed until the end of the follow-up period or within 30 days after the last study treatment in case of early subject withdrawal from the study. Subjects who had already participated in the current study and had either completed the study per protocol or had discontinued prematurely, were not allowed to be re-included.
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor | Ablynx NV | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Investigator Site | Los Angeles | California | 90033 | United States | ||
| Investigator Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33881463 | Derived | Peyvandi F, Cataland S, Scully M, Coppo P, Knoebl P, Kremer Hovinga JA, Metjian A, de la Rubia J, Pavenski K, Minkue Mi Edou J, De Winter H, Callewaert F. Caplacizumab prevents refractoriness and mortality in acquired thrombotic thrombocytopenic purpura: integrated analysis. Blood Adv. 2021 Apr 27;5(8):2137-2141. doi: 10.1182/bloodadvances.2020001834. | |
| 26863353 |
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Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
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76 subjects were screened, 75 subjects were randomized (= Intent-to-treat [ITT] population): 36 in the ALX-0081 group, 39 in the placebo group.
Subjects with aTTP were recruited from 11 countries in Europe, Australia, Asia and United States (US). Only adults were recruited; no adolescent patients were enrolled, although the trial was open for adolescent patients. A total of 75 patients were included in the trial.
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| ID | Title | Description |
|---|---|---|
| FG000 | Caplacizumab | Caplacizumab:
|
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 24, 2013 | Feb 25, 2019 |
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A single-blinded study design was initiated because, in the initial versions of the protocol, the dosing regimen could be adjusted dependent on the results of the Ristocetin Cofactor (RICO) test following the initial dose. Therefore, a double-blind design was not feasible because the results of the RICO test effectively unblinded the Investigator. Single-blind design was maintained due to the objective nature of the primary endpoint.
|
|
| Placebo | Biological |
|
|
| Number and Percentage of Subjects With Exacerbations of TTP | Number and percentage of subjects with exacerbations of TTP (defined as recurrent thrombocytopenia following a confirmed platelet count response and requiring a re-initiation of daily PE treatment after ≥ 1 day but ≤ 30 days of end of daily PE treatment. Time to first exacerbation of TTP was also examined as part of this end point analysis; the median time to first exacerbation could not be determined because of the small number of events. | Within 30 days of last day of initial daily PE |
| Number and Percentage of Subjects With Relapse of TTP | Number and percentage of subjects with relapse of TTP (defined as de novo TTP event that occurred later than 30 days after the last daily PE) was evaluated. | Later than 30 days after the last daily PE |
| Number of Daily PE Sessions During the Initial Daily PE Period | Number of daily PE sessions during the initial daily PE period which could include more than 1 PE per day was evaluated. | During the initial daily PE period, with a median (min, max) duration of exposure to study drug of 6 (2, 36) days |
| Total Volume of Plasma Administered During the Initial Daily PE Period | The total volume of plasma administered during the initial daily PE period was measured. | During the initial daily PE period, with a median (min, max) duration of exposure to study drug of 6 (2, 36) days |
| Number of Days With at Least One PE Administration During the Total Course of the Study | Number of days for PE was evaluated. This implies the number of days with at least one PE administration during the total course of the study. | During the total course of the study (from Screening till the 12-month follow-up [FU] visit) |
| The Maximum Number of Consecutive Days Per Subject Where There Was no Interruption of PE During the Initial Daily PE Period | The maximum number of consecutive days per subject where there was no interruption of PE during the initial daily PE period. | During the initial daily PE period, with a median (min, max) duration of exposure to study drug of 6 (2, 36) days |
| Resolution of Non-focal Neurological Symptoms | Resolution of non-focal neurological symptoms as defined by neurocognitive function at complete remission, measured by a Computerised Neuropsychological Test Battery(CNTB) (adults only). The CNTB included 6 modules: word list learning and selective reminding (WLL/SR), choice reaction time (CRT), visual memory (VMEM), simple reaction time (SRT), working memory (WMEM), and word list learning and delayed recall (WLL/DR). The 6 tasks are rated as a percentage correct (for CRT and SRT, the percentage correct corresponds to the percentage hits) and the mean score from these provides the CNTB summary score (range: 0-100). A higher CNTB summary score indicates better neuropsychological functioning. | From Baseline till the 12-month FU visit |
| Number of Participants With Resolution of TTP-related Signs or Symptoms | Resolution or improvement (improvement of ≥ 1 grade in the Common Terminology Criteria for Adverse Events [CTCAE] v4.0 scale) of TTP-related signs and symptoms as captured on physical examination and as adverse events. This endpoint was only evaluated for "resolution". | End of daily PE treatment period (median [min, max] duration of exposure to study drug of 6 [2, 36] days), end of study treatment period (median [min, max] duration of exposure to study drug of 36.5 [2, 90] days) and at 1 month follow-up |
| Mortality | Total mortality up to 1 month follow-up. | From the start of the study up to 1 month follow-up |
| Number of PE Related Adverse Events | Number of PE treatment-related adverse events (AEs). | From the start of the study up to 1 month follow-up |
| Number and Percentage of Subjects With PE Related AEs | Number and percentage of subjects with PE related AEs. | From the start of the study up to 1 month follow-up |
| Number of Treatment-emergent Adverse Events (TEAEs) by Severity | Number and severity of TEAEs were evaluated. The severity grades of AEs were defined as: mild, moderate, and severe. Note: the numbers listed do not include the TEAEs with missing severity. | From the start of the study up to 1 month follow-up |
| Number and Percentage of Subjects With TEAEs by Severity | Number and percentage of subjects with TEAEs by severity. The severity grades of AEs were defined as: mild, moderate, and severe. | From the start of the study up to 1 month follow-up |
| Number of TEAEs and Their Relationship to Study Drug | Number of TEAEs and their relationship to study drug were evaluated. Relationship of AEs to study drug was: related, possibly related, and unlikely/not related. | From the start of the study up to 1 month follow-up |
| Number of Participants Who Developed Treatment-emergent Anti-Drug Antibodies (ADA) | The development of anti-drug antibodies (ADA) was monitored from the start of the study until last follow-up visit. | From the start of the study until last follow-up visit |
| Plasma Concentrations of Caplacizumab | The concentration of caplacizumab in plasma was determined at different time points. pharmacokinetics (PK) Population: the PK Population consisted of all subjects who received the study drug and for whom the primary PK data are considered to be sufficient and interpretable. | From the start of the study up to 1 month follow-up (i.e., at Baseline, Days 1 and 2 of daily PE, last day of daily PE, Day 1 after daily PE, Weeks 1, 2, 3, and 4 after daily PE, Days 3 and 7 of FU and at the 1-month FU visit). |
| Pharmacodynamics (PD): Ristocetin Cofactor (RICO) Activity Over Time | The change from baseline in RICO activity was measured at different time points. | From the start of the study up to 1 month follow-up (i.e., at Baseline, Days 1 and 2 of daily PE, last day of daily PE, Day 1 after daily PE, Weeks 1, 2, 3, and 4 after daily PE, Days 3 and 7 of FU and at the 1-month FU visit). |
| Pharmacodynamics: Von Willebrand Factor Antigen (vWF:Ag) Over Time | The change from baseline in vWF:Ag concentration was measured at different time points. | From the start of the study drug up to 1 month follow-up (i.e., at Baseline, Days 1 and 2 of daily PE, last day of daily PE, Day 1 after daily PE, Weeks 1, 2, 3, and 4 after daily PE, Days 3 and 7 of FU and at the 1-month FU visit). |
| PD: Coagulation Factor VIII Clotting Activity (FVIII:C) Over Time | The change from baseline in FVIII:C concentration was measured at different ime points. | From the start of the study up to 1 month follow-up (i.e., at Baseline, Days 1 and 2 of daily PE, last day of daily PE, Day 1 after daily PE, Weeks 1, 2, 3, and 4 after daily PE, Days 3 and 7 of FU and at the 1-month FU visit). |
| Washington D.C. |
| District of Columbia |
| United States |
| Investigator Site | Atlanta | Georgia | 30322 | United States |
| Investigator Site | St Louis | Missouri | 63110 | United States |
| Investigator Site | New York | New York | 10021 | United States |
| Investigator Site | Rochester | New York | 14642 | United States |
| Investigator Site | Valhalla | New York | 10595 | United States |
| Investigator Site | Durham | North Carolina | 27710 | United States |
| Investigator Site | Winston-Salem | North Carolina | 27157 | United States |
| Investigator Site | Columbus | Ohio | 43210 | United States |
| Investigator Site | Pittsburgh | Pennsylvania | 15224 | United States |
| Investigator Site | Dallas | Texas | United States |
| Investigator Site | Salt Lake City | Utah | 84132 | United States |
| Investigator Site | Garran | Australian Capital Territory | Australia |
| Investigator Site | Liverpool | Australia |
| Investigator Site | Melbourne | Australia |
| Investigator Site | Woolloongabba | Australia |
| Investigator Site | Graz | Austria |
| Investigator Site | Vienna | Austria |
| Investigator Site | Antwerp | Belgium |
| Investigator Site | Brussels | Belgium |
| Investigator Site | Leuven | Belgium |
| Investigator Site | Namur | Belgium |
| Investigator Site | Sofia | Bulgaria |
| Investigator Site | Caen | France |
| Investigator Site | Ulm | Baden-Wurttemberg | Germany |
| Investigator Site | Aachen | Germany |
| Investigator Site | Berlin | Germany |
| Investigator Site | Cologne | Germany |
| Investigator Site | Dortmund | Germany |
| Investigator Site | Hanover | Germany |
| Investigator Site | Mainz | Germany |
| Investigator Site | Mannheim | Germany |
| Investigator Site | München | Germany |
| Investigator Site | Haifa | Israel |
| Investigator Site | Jerusalem | Israel |
| Investigator Site | Petah Tikva | Israel |
| Investigator Site | Catania | Italy |
| Investigator Site | Foggia | Italy |
| Investigator Site | Milan | Italy |
| Investigator Site | Reggio Emilia | Italy |
| Investigator Site | Rome | Italy |
| Investigator Site | Bucharest | Romania |
| Investigator Site | Badalona | Spain |
| Investigator Site | Seville | Spain |
| Investigator Site | Valencia | Spain |
| Investigator Site | Bern | Switzerland |
| Investigator Site | Lausanne | Switzerland |
| Investigator Site | Zurich | Switzerland |
| Investigator Site | Liverpool | United Kingdom |
| Investigator Site | London | United Kingdom |
| Peyvandi F, Scully M, Kremer Hovinga JA, Cataland S, Knobl P, Wu H, Artoni A, Westwood JP, Mansouri Taleghani M, Jilma B, Callewaert F, Ulrichts H, Duby C, Tersago D; TITAN Investigators. Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura. N Engl J Med. 2016 Feb 11;374(6):511-22. doi: 10.1056/NEJMoa1505533. |
| 22475545 | Derived | Holz JB. The TITAN trial--assessing the efficacy and safety of an anti-von Willebrand factor Nanobody in patients with acquired thrombotic thrombocytopenic purpura. Transfus Apher Sci. 2012 Jun;46(3):343-6. doi: 10.1016/j.transci.2012.03.027. Epub 2012 Apr 3. |
| FG001 | Placebo | Placebo:
|
| Received Study Drug |
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| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Caplacizumab | Caplacizumab:
|
| BG001 | Placebo | Placebo:
|
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Time-to-response of Treatment Defined by a Confirmed Recovery of Platelets ≥ 150,000/µL | Time-to-response, defined by the achievement of platelet count response, confirmed at 48 hours after the initial reporting of this response. Platelet response was defined as recovery of platelets ≥ 150,000/µL. This response had to be confirmed at 48 hours after the initial reporting of platelet recovery ≥ 150,000/µL by a de novo measure of platelets ≥ 150,000/µL and lactate dehydrogenase (LDH) ≤ 2x upper limit of normal (ULN) (i.e., 'confirmed platelet response'). | ITT Population | Posted | Median | 95% Confidence Interval | days | From the day of first study drug administration up to 30 days after first study drug administration |
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| Secondary | Number and Percentage of Subjects With Complete Remission Following Initial Daily Plasma Exchange (PE) | Number and percentage of subjects with complete remission (defined as confirmed platelet count response and absence of exacerbation) following initial daily PE. | ITT Population | Posted | Count of Participants | Participants | From the day of first study drug administration up to 30 days after first study drug administration |
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| Secondary | Number and Percentage of Subjects With Exacerbations of TTP | Number and percentage of subjects with exacerbations of TTP (defined as recurrent thrombocytopenia following a confirmed platelet count response and requiring a re-initiation of daily PE treatment after ≥ 1 day but ≤ 30 days of end of daily PE treatment. Time to first exacerbation of TTP was also examined as part of this end point analysis; the median time to first exacerbation could not be determined because of the small number of events. | ITT Population | Posted | Count of Participants | Participants | Within 30 days of last day of initial daily PE |
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| Secondary | Number and Percentage of Subjects With Relapse of TTP | Number and percentage of subjects with relapse of TTP (defined as de novo TTP event that occurred later than 30 days after the last daily PE) was evaluated. | ITT Population | Posted | Count of Participants | Participants | Later than 30 days after the last daily PE |
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| Secondary | Number of Daily PE Sessions During the Initial Daily PE Period | Number of daily PE sessions during the initial daily PE period which could include more than 1 PE per day was evaluated. | Number of subjects from the ITT Population with data available | Posted | Mean | Standard Deviation | PE sessions | During the initial daily PE period, with a median (min, max) duration of exposure to study drug of 6 (2, 36) days |
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| Secondary | Total Volume of Plasma Administered During the Initial Daily PE Period | The total volume of plasma administered during the initial daily PE period was measured. | Number of subjects from the ITT Population with data available | Posted | Mean | Standard Deviation | mL | During the initial daily PE period, with a median (min, max) duration of exposure to study drug of 6 (2, 36) days |
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| Secondary | Number of Days With at Least One PE Administration During the Total Course of the Study | Number of days for PE was evaluated. This implies the number of days with at least one PE administration during the total course of the study. | Number of subjects from the ITT Population with data available | Posted | Mean | Standard Deviation | days | During the total course of the study (from Screening till the 12-month follow-up [FU] visit) |
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| Secondary | The Maximum Number of Consecutive Days Per Subject Where There Was no Interruption of PE During the Initial Daily PE Period | The maximum number of consecutive days per subject where there was no interruption of PE during the initial daily PE period. | Number of subjects from the ITT Population with data available | Posted | Mean | Standard Deviation | days | During the initial daily PE period, with a median (min, max) duration of exposure to study drug of 6 (2, 36) days |
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| Secondary | Resolution of Non-focal Neurological Symptoms | Resolution of non-focal neurological symptoms as defined by neurocognitive function at complete remission, measured by a Computerised Neuropsychological Test Battery(CNTB) (adults only). The CNTB included 6 modules: word list learning and selective reminding (WLL/SR), choice reaction time (CRT), visual memory (VMEM), simple reaction time (SRT), working memory (WMEM), and word list learning and delayed recall (WLL/DR). The 6 tasks are rated as a percentage correct (for CRT and SRT, the percentage correct corresponds to the percentage hits) and the mean score from these provides the CNTB summary score (range: 0-100). A higher CNTB summary score indicates better neuropsychological functioning. | The Computerized Neuropsychological Test Battery (CNTB) was completed by a low proportion of subjects with baseline data available for only 3 subjects in the caplacizumab and 4 subjects in the placebo group and 12 month post-discharge data available for 10 and 6 subjects, respectively. | Posted | Mean | Standard Deviation | score on a scale | From Baseline till the 12-month FU visit |
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| Secondary | Number of Participants With Resolution of TTP-related Signs or Symptoms | Resolution or improvement (improvement of ≥ 1 grade in the Common Terminology Criteria for Adverse Events [CTCAE] v4.0 scale) of TTP-related signs and symptoms as captured on physical examination and as adverse events. This endpoint was only evaluated for "resolution". | ITT Population | Posted | Count of Participants | Participants | End of daily PE treatment period (median [min, max] duration of exposure to study drug of 6 [2, 36] days), end of study treatment period (median [min, max] duration of exposure to study drug of 36.5 [2, 90] days) and at 1 month follow-up |
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| Secondary | Mortality | Total mortality up to 1 month follow-up. | ITT Population | Posted | Count of Participants | Participants | From the start of the study up to 1 month follow-up |
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| Secondary | Number of PE Related Adverse Events | Number of PE treatment-related adverse events (AEs). | ITT Population | Posted | Number | adverse events | From the start of the study up to 1 month follow-up |
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| Secondary | Number and Percentage of Subjects With PE Related AEs | Number and percentage of subjects with PE related AEs. | ITT Population | Posted | Count of Participants | Participants | From the start of the study up to 1 month follow-up |
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| Secondary | Number of Treatment-emergent Adverse Events (TEAEs) by Severity | Number and severity of TEAEs were evaluated. The severity grades of AEs were defined as: mild, moderate, and severe. Note: the numbers listed do not include the TEAEs with missing severity. | Safety Population | Posted | Number | adverse events | From the start of the study up to 1 month follow-up |
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| Secondary | Number and Percentage of Subjects With TEAEs by Severity | Number and percentage of subjects with TEAEs by severity. The severity grades of AEs were defined as: mild, moderate, and severe. | Safety Population | Posted | Count of Participants | Participants | From the start of the study up to 1 month follow-up |
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| Secondary | Number of TEAEs and Their Relationship to Study Drug | Number of TEAEs and their relationship to study drug were evaluated. Relationship of AEs to study drug was: related, possibly related, and unlikely/not related. | Safety Population | Posted | Number | adverse events | From the start of the study up to 1 month follow-up |
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| Secondary | Number of Participants Who Developed Treatment-emergent Anti-Drug Antibodies (ADA) | The development of anti-drug antibodies (ADA) was monitored from the start of the study until last follow-up visit. | Number of subjects from the Safety Population with data available | Posted | Count of Participants | Participants | From the start of the study until last follow-up visit |
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| Secondary | Plasma Concentrations of Caplacizumab | The concentration of caplacizumab in plasma was determined at different time points. pharmacokinetics (PK) Population: the PK Population consisted of all subjects who received the study drug and for whom the primary PK data are considered to be sufficient and interpretable. | PK Population, no PK data were generated for the subjects in the placebo group | Posted | Mean | Standard Error | ng/mL | From the start of the study up to 1 month follow-up (i.e., at Baseline, Days 1 and 2 of daily PE, last day of daily PE, Day 1 after daily PE, Weeks 1, 2, 3, and 4 after daily PE, Days 3 and 7 of FU and at the 1-month FU visit). |
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| Secondary | Pharmacodynamics (PD): Ristocetin Cofactor (RICO) Activity Over Time | The change from baseline in RICO activity was measured at different time points. | Safety Population | Posted | Mean | Standard Deviation | percentage of RICO activity | From the start of the study up to 1 month follow-up (i.e., at Baseline, Days 1 and 2 of daily PE, last day of daily PE, Day 1 after daily PE, Weeks 1, 2, 3, and 4 after daily PE, Days 3 and 7 of FU and at the 1-month FU visit). |
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| Secondary | Pharmacodynamics: Von Willebrand Factor Antigen (vWF:Ag) Over Time | The change from baseline in vWF:Ag concentration was measured at different time points. | Safety Population | Posted | Mean | Standard Deviation | Percentage of vWF:Ag | From the start of the study drug up to 1 month follow-up (i.e., at Baseline, Days 1 and 2 of daily PE, last day of daily PE, Day 1 after daily PE, Weeks 1, 2, 3, and 4 after daily PE, Days 3 and 7 of FU and at the 1-month FU visit). |
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| Secondary | PD: Coagulation Factor VIII Clotting Activity (FVIII:C) Over Time | The change from baseline in FVIII:C concentration was measured at different ime points. | Safety Population | Posted | Mean | Standard Deviation | Percentage of FVIII:C activity | From the start of the study up to 1 month follow-up (i.e., at Baseline, Days 1 and 2 of daily PE, last day of daily PE, Day 1 after daily PE, Weeks 1, 2, 3, and 4 after daily PE, Days 3 and 7 of FU and at the 1-month FU visit). |
|
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From time of the first study drug administration up to the last follow-up visit (12 months)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Caplacizumab | Caplacizumab 10 mg once daily | 0 | 35 | 20 | 35 | 33 | 35 |
| EG001 | Placebo | Placebo once daily | 2 | 37 | 19 | 37 | 37 | 37 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombotic thrombocytopenic purpura | Blood and lymphatic system disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Anemia | Blood and lymphatic system disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Atrial flutter | Cardiac disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Retinal hemorrhage | Eye disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Hypertransaminasemia | Hepatobiliary disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Bacterial infection | Infections and infestations | MedDRA (16.1) | Systematic Assessment |
| |
| Muscle abscess | Infections and infestations | MedDRA (16.1) | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA (16.1) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (16.1) | Systematic Assessment |
| |
| Device related sepsis | Infections and infestations | MedDRA (16.1) | Systematic Assessment |
| |
| Traumatic fracture | Injury, poisoning and procedural complications | MedDRA (16.1) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (16.1) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (16.1) | Systematic Assessment |
| |
| Autoantibody test | Investigations | MedDRA (16.1) | Systematic Assessment |
| |
| Transaminases increased | Investigations | MedDRA (16.1) | Systematic Assessment |
| |
| Liver function test abnormal | Investigations | MedDRA (16.1) | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Transient ischemic attack | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Dysarthria | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Paresthesia | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Subarachnoid hemorrhage | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Cerebral hemorrhage | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Facial paresis | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Mental status changes | Psychiatric disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Substance-induced psychotic disorder | Psychiatric disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Hematuria | Renal and urinary disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Metrorrhagia | Reproductive system and breast disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Prostatitis | Reproductive system and breast disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Dermatitis allergic | Skin and subcutaneous tissue disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA (16.1) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Leukocytosis | Blood and lymphatic system disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Neutrophilia | Blood and lymphatic system disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Acute myocardial infarction | Cardiac disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Cardiac disorder | Cardiac disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Diplopia | Eye disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Gingival bleeding | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Paraesthesia oral | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Catheter site pain | General disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Chills | General disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Injection site bruising | General disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Injection site hemorrhage | General disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Local swelling | General disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Edema peripheral | General disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Pain | General disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA (16.1) | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA (16.1) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (16.1) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (16.1) | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA (16.1) | Systematic Assessment |
| |
| Transfusion reaction | Injury, poisoning and procedural complications | MedDRA (16.1) | Systematic Assessment |
| |
| Activated partial thromboplastin time prolonged | Investigations | MedDRA (16.1) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (16.1) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (16.1) | Systematic Assessment |
| |
| Blood lactate dehydrogenase increased | Investigations | MedDRA (16.1) | Systematic Assessment |
| |
| Blood potassium decreased | Investigations | MedDRA (16.1) | Systematic Assessment |
| |
| Brain natriuretic peptide increased | Investigations | MedDRA (16.1) | Systematic Assessment |
| |
| C-reactive protein increased | Investigations | MedDRA (16.1) | Systematic Assessment |
| |
| Hemoglobin decreased | Investigations | MedDRA (16.1) | Systematic Assessment |
| |
| Haptoglobin decreased | Investigations | MedDRA (16.1) | Systematic Assessment |
| |
| Neutrophil count increased | Investigations | MedDRA (16.1) | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA (16.1) | Systematic Assessment |
| |
| White blood cell count increased | Investigations | MedDRA (16.1) | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Fluid retention | Metabolism and nutrition disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Hyperglycemia | Metabolism and nutrition disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Hypocalcemia | Metabolism and nutrition disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Hypokalemia | Metabolism and nutrition disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Disturbance in attention | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Migraine | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Transient ischemic attack | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Agitation | Psychiatric disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Disorientation | Psychiatric disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Restlessness | Psychiatric disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Sleep disorder | Psychiatric disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Menorrhagia | Reproductive system and breast disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Metrorrhagia | Reproductive system and breast disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Hematoma | Vascular disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Phlebitis | Vascular disorders | MedDRA (16.1) | Systematic Assessment |
|
The study was stopped prematurely before meeting its enrollment target. The study is not considered to have been terminated as sites were requested to perform the assessments until 1-month follow-up if they had subjects in the study.
Publication of any results from this study will be according to the principles of the Declaration of Helsinki, in particular point 30, and will require prior review and written agreement of the Sponsor.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Monitor | Ablynx | +32 (9) 262 00 00 | clinicaltrials@ablynx.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Dec 9, 2013 | Feb 25, 2019 | SAP_001.pdf |
| ID | Term |
|---|---|
| D011697 | Purpura, Thrombotic Thrombocytopenic |
| ID | Term |
|---|---|
| D011696 | Purpura, Thrombocytopenic |
| D011693 | Purpura |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D057049 | Thrombotic Microangiopathies |
| D013921 | Thrombocytopenia |
| D001791 | Blood Platelet Disorders |
| D000095542 | Cytopenia |
| D019851 | Thrombophilia |
| D006470 | Hemorrhage |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012877 | Skin Manifestations |
| D012816 | Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| C585343 | caplacizumab |
Not provided
Not provided
Not provided
| >=65 years |
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| Male |
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| Black |
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